<i>Insm2</i> deficiency results in female infertility by disturbing steroid pathway and decreasing ovarian reserve in mice.

The number and quality of oocytes in the ovarian reserve are related to fertility and reproductive lifespan in mammals. Some transcription factors have been demonstrated to determine oogenesis. The insulinoma-associated 2 (<i>Insm2</i>) gene is a member of the Snail transcriptional repressor superfamily. Recent studies have demonstrated <i>Insm2</i> plays an essential role for insulin secretion and glucose intolerance in mice, but the functions of <i>Insm2</i> in reproduction remain elusive. Here, by examination of <i>Insm2</i> knockout mice, we found <i>Insm2</i> was essential for female fertility. Loss of <i>Insm2</i> resulted in female infertility with major defects in primordial follicle pool, ovarian folliculogenesis and ovulation. Transcriptomic profiling of ovaries suggests that loss of <i>Insm2</i> caused defects in oocyte meiosis and steroid synthesis. Both oocyte- and granulosa cell-expressed genes were dysregulated, including <i>Foxo1</i> and other known genes involved in primary ovarian insufficiency. Together, these studies show that <i>Insm2</i> is required for oocyte development and their communication with ovarian somatic cells.